ABCG2: the key to chemoresistance in cancer stem cells?

An, Yi; Ongkeko, Weg M.

doi:10.1517/17425250903228834

Cited by 142 publications

(90 citation statements)

References 127 publications

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“…[45][46][47] Similarly, the expression of ABC transporters including P-gp was detected in B16F10 cells. [48][49][50] Therefore, based on the above information, it can be concluded that in the case of G-II cells, efflux pumps play an active role in mediating their sensitivities to DOX in a drug-concentration dependent manner.…”

Section: Discussionmentioning

confidence: 97%

Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Kibria

Hatakeyama

Akiyama

et al. 2014

Biological & Pharmaceutical Bulletin

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Multi-drug resistance (MDR) of cancers to chemotherapy including doxorubicin (DOX) is mediated by several factors. To design an effective therapy for the treatment of chemotherapy-resistant cancers, it is essential to explore the elements responsible for mediating MDR. However, exploring these factors in detail in a wide range of tumor types is challenging as several critical analytical steps are involved. Here, we demonstrated the way of exploring the factors mediating MDR in the tumor types without performing the analysis at the molecular level of cells. The sensitivities of 15 different types of cancer cells to DOX were evaluated, and the role of P-glycoprotein (P-gp), one of the major efflux-pumps, was explored. A correlation curve was developed between the intracellular amounts of DOX and the sensitivities of cells, and, based on this correlation, the cells were classified in response to the involvement of P-gp that mediates MDR. P-gp plays an active role in mediating MDR of cancer cells where a correlation between the sensitivities of cells and the accumulated DOX exists. In contrast, in cells that show a resistance to DOX but whose sensitivities are independent of the amount of accumulated drug, it was reasonably presumed that mechanisms other than P-gp are likely to be involved in mediating MDR. Based on the correlation between the availability of a drug and cell sensitivity, it would be reasonable to explore the factors governing cancer MDR, which is essential in designing an effective therapeutic approach for treating chemotherapy-resistant cancers using chemotherapeutic drugs.

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Section: Discussionmentioning

confidence: 97%

Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Kibria

Hatakeyama

Akiyama

et al. 2014

Biological & Pharmaceutical Bulletin

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show abstract

“…Its role in chemoresistance has also been studied in breast carcinoma, non-small-cell lung carcinoma, oral squamous cell carcinoma and advanced testicular germ cell tumors. 20 Contradictory results have been found regarding its expression in melanoma cell lines. 21,22 Deichmann et al 21 studied 18 melanoma resection specimens and could not demonstrate ABCG2 mRNA upregulation by reverse transcriptase polymerase chain reaction, while Monzani et al 22 found in vitro and in vivo ABCG2 expression in all the cells expressing CD133 by reverse transcriptase polymerase chain reaction and immunohistochemistry.…”

Section: Discussionmentioning

confidence: 99%

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma

et al. 2012

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Distinct ABCB5 forms and ABCF2, members of the ATP-binding cassette (ABC) superfamily of transporters, are normally expressed in various tissues and cells, and enhanced expression of both has been demonstrated in select cancers. In melanoma cell lines, gene expression profiling of ABC transporters has revealed enhanced expression of melanocyte-specific ABCB5 and ABCF2 proteins. Given this, our primary aim was to ascertain immunohistochemical expression of the ABC transporters ABCB5 and ABCF2 and, the stem cell marker, nestin in a spectrum of benign and malignant nevomelanocytic proliferations, including nevi (n ¼ 30), in situ (n ¼ 31) and invasive (n ¼ 24) primary cutaneous melanomas to assess their role in the stepwise development of malignancy. In addition, their expression was compared with established melanoma prognosticators to ascertain their utility as independent prognosticators. A semiquantitative scoring system was utilized by deriving a cumulative score (based on percentage positivity cells and intensity of expression) and statistical analyses was carried out using analysis of variance with linear contrasts. Mean cumulative score in nevi, in situ and invasive melanoma were as follows: 3.8, 4.4 and 5.3 for ABCB5, respectively (Po0.005 for all), and 4.6, 4.6 and 5.3 for nestin, respectively (P ¼ not significant for all). No appreciable expression of ABCF2 was noted in any of the groups. While ulcerated lesions of melanoma demonstrated lower levels of expression of ABCB5 and nestin than non-ulcerated lesions, and nestin expression was lower in lesions with mitoses 41, after controlling for the presence of ulceration and mitotic activity, the expression of both proteins did not significantly correlate with known melanoma prognosticators. The gradual increase in the expression of ABCB5 from benign nevus to in situ to invasive melanoma suggests that it plays a role in melanomagenesis. On the basis of our findings, a prospective study with follow-up data is required to ascertain the utility of ABCB5 as a therapeutic target.

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“…IL-6 and IL-8 are autocrine growth factors for MPM. 35,36 Finally, we found reduced levels of the drug transporter ABCG2, a drug efflux pump responsible for multidrug resistance (MDR) of several solid and non-solid tumors 52 ( Fig. 3A) (Fig.…”

Section: Butein Affects the Resistance Of Mpm Cells To Pemetrexedmentioning

confidence: 92%

Butein impairs the protumorigenic activity of malignant pleural mesothelioma cells

et al. 2012

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ABCG2: the key to chemoresistance in cancer stem cells?

Cited by 142 publications

References 127 publications

Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Comparative Study of the Sensitivities of Cancer Cells to Doxorubicin, and Relationships between the Effect of the Drug-Efflux Pump P-gp

Profiling of ABC transporters ABCB5, ABCF2 and nestin-positive stem cells in nevi, in situ and invasive melanoma

Butein impairs the protumorigenic activity of malignant pleural mesothelioma cells

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